Robyn Banerjee

Framework for the quantitative assessment of adaptive radiation therapy protocols

Abstract Background Adaptive radiation therapy (ART) “flags,” such as change in external body contour or relative weight loss, are widely used to identify which head and neck cancer (HNC) patients may benefit from replanned treatment. Despite the popularity of ART, few published quantitative approaches verify the accuracy of replan candidate identification, especially with regards to the simple flagging approaches that are considered current standard of practice. We propose a quantitative evaluation framework, demonstrated through the assessment of a single institutions clinical ART flag: change in body contour exceeding 1.5 cm. Methods Ground truth replan criteria were established by surveying HNC radiation oncologists. Patient‐specific dose deviations were approximated by using weekly acquired CBCT images to deform copies of the CT simulation, yielding during treatment “synthetic CTs.” The original plan reapplied to the synthetic CTs estimated interfractional dose deposition and truth table analysis compared ground truth flagging with the clinical ART metric. This process was demonstrated by assessing flagged fractions for 15 HNC patients whose body contour changed by >1.5 cm at some point in their treatment. Results Survey results indicated that geometric shifts of high‐dose volumes relative to image‐guided radiation therapy alignment of bony anatomy were of most interest to HNC physicians. This evaluation framework successfully identified a fundamental discrepancy between the “truth” criteria and the body contour flagging protocol selected to identify changes in central axis dose. The body contour flag had poor sensitivity to survey‐derived major violation criteria (0%–28%). The sensitivity of a random sample for comparable violation/flagging frequencies was 27%. Conclusions These results indicate that centers should establish ground truth replan criteria to assess current standard of practice ART protocols. In addition, more effective replan flags may be tested and identified according to the proposed framework. Such improvements in ART flagging may contribute to better clinical resource allocation and patient outcome.

Anemia, leukocytosis and thrombocytosis as prognostic factors in patients with cervical cancer treated with radical chemoradiotherapy: A retrospective cohort study

Introduction Anemia has long been associated with poor prognosis in patients with cervical cancer. Recently, additional hematologic parameters have emerged as potential indicators of worse outcome in this patient group. In a cohort of cervical cancer patients treated with chemoradiotherapy (CRT) and brachytherapy, we report on the prognostic significance of hematologic parameters including anemia, leukocytosis, neutrophil to lymphocyte ratio (NLR), and thrombocytosis, the effect of combining anemia with other hematologic parameters, and the effect of changes in hemoglobin levels during treatment. Materials and methods Two-hundred fifty-seven cervical cancer patients were retrospectively identified from a single cancer institution’s database. Hematologic parameters were categorized as: anemia (hemoglobin ≤115 g/L), leukocytosis (white blood cell count >10 × 109/L), thrombocytosis (platelets >400 × 109/L), and NLR (ratio >5). The association between clinical factors and hematologic parameters on progression-free survival (PFS) and overall survival (OS) were assessed at 5 years. Results At 5 years, both pre-treatment anemia (PFS: 60% vs 34%, p < 0.0001; OS: 68% vs 41%, p < 0.0001) and on-treatment anemia (PFS: 62% vs 40%, p < 0.0001; OS: 70% vs 48%, p < 0.0001) were significantly associated with worse survival. This adverse effect on 5-year PFS and OS was increased in patients with both pre-treatment anemia and leukocytosis (PFS: 72% vs 42%, p < 0.0001; OS: 68% vs 37%, p < 0.0001) and pre-treatment anemia and elevated NLR (PFS: 61% vs 30%, p < 0.0001; OS: 68% vs 37%, p < 0.0001). Five-year PFS (50% vs 31%) and OS (60% vs 36%) was better in patients whose pre-treatment anemia improved to normal hemoglobin levels on treatment vs those patients who were anemic both pre- and on-treatment. Conclusion Pre-treatment and on-treatment anemia were significant, independent predictors of worse PFS and OS. Anemia and other hematologic parameters remain prognostic markers for cervical cancer patients. Improvement in PFS and OS was seen in patients with normalization of hemoglobin.

Letter to the Editor regarding: "Treatment patterns and survival outcomes in patients with cervical cancer complicated by complete uterine prolapse: a systematic review of literature".

Sir, We read with interest the review by Matsuo et al. of case reports regarding treatment of cervical cancer in the setting of procidentia [1]. We compliment the authors for highlighting a rare but complex clinical scenario. However, the data presented do not support their conclusion that, compared with primary radiation, Bsurgery-based treatment may have a positive effect on survival outcome in cervical cancer patients with complete uterine prolapse^. Such a conclusion would necessitate controlling for key patient and treatment variables including staging methodology, lymph node status, radiotherapy dose, target volume, and chemotherapy use. Tumor size is only reported in 16 of 78 patients. One-quarter of the patients treated with radiation alone received whole pelvic radiotherapy without brachytherapy. This is by definition palliative intent treatment and should not be compared with curative-intent therapies. Chemotherapy use is not controlled for, although concurrent chemoradiotherapy has been established as standard of care in patients with locally advanced cervical cancer since 2000 [2]. Finally, the authors’ contention that Bsurgerybased treatment was associated with significantly better disease-specific overall survival^ cannot be supported given that the cause of death was Bnot stated^ in the majority of patients (49 of 78). Given the rarity of these coexisting conditions it is unsurprising that treatment approaches are heterogeneous. This very fact, however, undermines the ability to draw a robust conclusion about the relative merits of radiation versus surgical approaches in this scenario. Despite this, we would argue that because of the practical difficulties in delivering curative-intent radiotherapy in the setting of procidentia (due to challenges in target delineation, daily set-up reproducibility, and feasibility of brachytherapy treatment), surgery should be considered as the first-line approach in this setting.

SU-E-T-509: Inter-Observer and Inter-Modality Contouring Analysis for Organs at Risk for HDR Gynecological Brachytherapy

Purpose This study quantifies errors associated with MR-guided High Dose Rate (HDR) gynecological brachytherapy. Uncertainties in this treatment results from contouring, organ motion between imaging and treatment delivery, dose calculation, and dose delivery. We focus on interobserver and inter-modality variability in contouring and the motion of organs at risk (OARs) in the time span between the MR and CT scans (∼1 hour). We report the change in organ volume and position of center of mass (CM) between the two imaging modalities. Methods A total of 8 patients treated with MR-guided HDR brachytherapy were included in this study. Two observers contoured the bladder and rectum on both MR and CT scans. The change in OAR volume and CM position between the MR and CT imaging sessions on both image sets were calculated. Results The absolute mean bladder volume change between the two imaging modalities is 67.1cc. The absolute mean inter-observer difference in bladder volume is much lower at 15.5cc (MR) and 11.0cc (CT). This higher inter-modality volume difference suggests a real change in the bladder filling between the two imaging sessions. Change in Rectum volume inter-observer standard error of means (SEM) is 3.18cc (MR) and 3.09cc (CT), while the inter-modality SEM is 3.65cc (observer 1), and 2.75cc (observer 2). The SEM for rectum CM position in the superior-inferior direction was approximately three times higher than in other directions for both the inter—observer (0.77 cm, 0.92 cm for observers 1 and 2, respectively) and inter-modality (0.91 cm, 0.95 cm for MR and CT, respectively) variability. Conclusion Bladder contours display good consistency between different observers on both CT and MR images. For rectum contouring the highest inconsistency stems from the observers’ choice of the superior-inferior borders. A complete analysis of a larger patient cohort will enable us to separate the true organ motion from the inter-observer variability.

SU‐E‐T‐343: Dosimetric Analysis of Catheter Displacement in High Dose Rate Prostate Brachytherapy

PURPOSE To evaluate the dosimetric effect of catheter displacement on target coverage and doses to organs at risks (OARs) in high dose rate prostate brachytherapy. METHODS CT simulations from 21 prostate cancer patients treated with HDR monotherapy (7.25 Gy × 6 fractions) were used. The prostate CTV and OARs were contoured on the 3D-CT. Treatment plans were optimized using an inverse planning simulated annealing algorithm and graphical optimization to ensure dosimetry objectives: target coverage (CTV D90=100-115%, V100 >97%, and V150 <35%) and OAR dose constraints (D0.1cc <85% (rectum), 80&-95% (bladder), and <110% (urethra)). Craniocaudal catheter movements from 1 to 10 mm in 1 mm increments were simulated by simultaneously shifting all active dwell positions in the initial treatment plan using catheter offset in the Oncentra MasterPlan (Nucletron). Target coverage (D90 and V100) and OAR doses (D0.1cc and D1cc) were evaluated and compared to no displacement plans. RESULTS The mean prostate CTV volume was 74.7±22.8 cc (range: 24.8-113.7 cc). Initial treatment plans provided target D90 = 107.7±2.0% (103.0-111.2%) and V100 = 98.5±0.8% (97.1-99.5%). The D0.1cc to OARs was 77.3±2.3% (rectum), 84.2±2.0% (bladder), and 106.8±1.6% (urethra). The mean target coverage was not significantly different for 1-2 mm shifts. Shifts between 3 and 6 mm still met most dosimetry objectives, but provided progressively less good target coverage and doses to OARs. Displacements of greater than or equal to 7 mm resulted in dosimetry that did not meet our dosimetry objectives. CONCLUSION Small changes in catheter position Result in significant alterations in dosimetry and treatment delivery. The target coverage (D90 and V100) and bladder dose are reduced and the rectal and urethra doses are higher in direct proportion to the degree of displacement. It is essential to check and correct interstitial catheter positions before each HDR fraction to accurately deliver the planned radiation dose.